A study of therapy and prevention in a Vietnamese cohort of HIV-1 infection

• Project/Area Number: 15H02658
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Infectious disease medicine
• Research Institution: Kumamoto University
• Principal Investigator: TAKIGUCHI Masafumi 熊本大学, エイズ学研究センター, 教授 (00183450)
• Co-Investigator(Kenkyū-buntansha): 岡 慎一 国立研究開発法人国立国際医療研究センター, エイズ治療・研究開発センター, センター長 (20194326)
• Research Collaborator: MURAKOSHI Hayato ; KUSE Nozomi ; AKAHOSHI Tomohiro ; CHIKATA Takayuki
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥42,120,000 (Direct Cost: ¥32,400,000、Indirect Cost: ¥9,720,000); Fiscal Year 2018: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2017: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2016: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000); Fiscal Year 2015: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: HIV-1 / エイズ / ベトナムコホート / 感染症 / ＨＩＶ－１

Outline of Final Research Achievements

We analyzed the association of HLA with clinical outcome in 536 HIV-1 subtype A/E-infected treatment-naive Vietnamese and found that HLA-C*12:02 and HLA-A*29:01-B*07:05-C*15:05 were protective allele and detrimental haplotype, respectively. We further analyzed the sequences of HIV-1 in these individuals and identified 303 HLA-associated mutations which are candidates of CTL escape mutations.
We analyzed ART treatment patients and found 90% success rate of treatment for 42 months. Out of 26 patients with treatment failure, 5 patients were infected with HIV-1 having drug resistance mutations in protease. We also found a significant association of TPVr treatment with hyperlipidemia in the treatment patients.

Academic Significance and Societal Importance of the Research Achievements

本研究により、HIV-1サブタイプA/E慢性感染者で、エイズ進行に関与するHLAを同定できた。また、初めてHIV-1サブタイプA/Eに対する免疫逃避変異を明らかにでき、HIV-1増殖抑制能を有したCTLを明らかにできたことは、今後のHIV-1サブタイプA/Eに対するワクチン開発に貢献できる。治療患者の解析では、ベトナムでも日本と同じレベルの治療効果が得られたが、プロテアーゼ阻害剤に対する薬剤耐性変異が確認され、今後このような薬剤耐性ウイルスが広まることが危惧された。

Research Products

• [Int'l Joint Research] NHTD, Hanoi(ベトナム)
• [Int'l Joint Research] NHTD, Hanoi(ベトナム)
• [Int'l Joint Research] NIH(米国)
• [Int'l Joint Research] NHTD, Hanoi(ベトナム)
• [Journal Article] The role of conventional antibodies targeting the CD4 binding site and CD4-induced epitopes in the control of HIV-1 CRF01_AE viruses. (2019)
  • Author(s): Thida W, Kuwata T, Maeda Y, Yamashiro T, Tran GV, Nguyen KV, Takiguchi M, Gatanaga H, Tanaka K, Matsushita S
  • Journal Title: Biochem Biophys Res Commun Volume: 508 Issue: 1 Pages: 46-51
  • DOI: 10.1016/j.bbrc.2018.11.063
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effective suppression of HIV-1 replication by CTLs specific for Pol epitopes in conserved mosaic vaccine immunogens (2019)
  • Author(s): Zou C*, Murakoshi H*, Kuse N, Akahoshi T, Chikata T, Gatanaga H, Oka S, Hanke T, Takiguchi M (*Equal contribution)
  • Journal Title: Journal of Virology Volume: 93 Issue: 7
  • DOI: 10.1128/jvi.02142-18
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Broad Recognition of Circulating HIV-1 by HIV-1-Specific Cytotoxic T-Lymphocytes with Strong Ability to Suppress HIV-1 Replication (2019)
  • Author(s): Murakoshi H*, Kuse N*, Akahoshi T, Zhang Y, Chikata T, Borghan MA, Gatanaga H, Oka S, Sakai K, Takiguchi M (* equal contribution)
  • Journal Title: Journal of Virology Volume: 93 Issue: 1
  • DOI: 10.1128/jvi.01480-18
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] CD8+ T cells specific for conserved, cross-reactive Gag epitopes with strong ability to suppress HIV-1 replication (2018)
  • Author(s): Murakoshi H*, Zou C*, Kuse N, Akahoshi T, Chikata T, Gatanaga H, Oka S, Hanke T, Takiguchi M (* equal contribution)
  • Journal Title: Retrovirology Volume: 15 Issue: 1 Pages: 46-46
  • DOI: 10.1186/s12977-018-0429-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tenofovir disoproxil fumarate co-administered with lopinavir/ritonavir is strongly associated with tubular damage and chronic kidney disease (2018)
  • Author(s): Mizushima Daisuke、Nguyen Dung Thi Hoai、Nguyen Dung Thi、Matsumoto Shoko、Tanuma Junko、Gatanaga Hiroyuki、Trung Nguyen Vu、van Kinh Nguyen、Oka Shinichi
  • Journal Title: Journal of Infection and Chemotherapy Volume: 24 Issue: 7 Pages: 549-554
  • DOI: 10.1016/j.jiac.2018.03.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] HLA Class I-Mediated HIV-1 Control in Vietnamese Infected with HIV-1 Subtype A/E (2017)
  • Author(s): Chikata Takayuki、Tran Giang Van、Murakoshi Hayato、Akahoshi Tomohiro、Qi Ying、Naranbhai Vivek、Kuse Nozomi、Tamura Yoshiko、Koyanagi Madoka、Sakai Sachiko、et al.
  • Journal Title: Journal of Virology Volume: 92 Issue: 5
  • DOI: 10.1128/jvi.01749-17
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Potential for immune-driven viral polymorphisms to compromise antiretroviral-based preexposure prophylaxis for prevention of HIV-1 infection (2017)
  • Author(s): Gatanaga H, Brumme ZL, Adland E, Reyes-Teran G, Avila-Rios S, Mejia-Villatoro CR, Hayashida T, Chikata T, Van Tran G, Van Nguyen K, Meza RI, Palou EY, Valenzuela-Ponce H, Pascale JM, Porras-Cortes G, Manzanero M, Lee GQ, Martin JN, Carrington MN, John M, Mallal S, Poon AFY, Goulder P, Takiguchi M, Oka S
  • Journal Title: AIDS Volume: 31 Issue: 14 Pages: 1935-1943
  • DOI: 10.1097/qad.0000000000001575
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam (2017)
  • Author(s): Tanuma J, Matsumoto S, Haneuse S, Cuong DD, Vu TV, Thuy PTT, Dung NT, Dung NTH, Trung NV, Kinh NV, Oka S
  • Journal Title: Journal of the International AIDS Society Volume: 20 Issue: 4
  • DOI: 10.1002/jia2.25030
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Social Support as a Key Protective Factor against Depression in HIV-Infected Patients: Report from large HIV clinics in Hanoi, Vietnam (2017)
  • Author(s): Matsumoto S, Yamaoka K, Takahashi K, Tanuma J, Mizushima D, Do CD, Nguyen DT, Nguyen HDT, Nguyen KV, Oka S
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 15489-15489
  • DOI: 10.1038/s41598-017-15768-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A strong association of HLA-associated Pol and Gag mutations with clinical parameters (2016)
  • Author(s): Giang Van Tran,* Takayuki Chikata,* Jonathan M. Carson, Hayato Murakoshi, Dung Hoai Nguyen, Yoshiko Tamura, Tomohiro Akahoshi, Nozomi Kuse, Keiko Sakai, Sachiko Sakai, Kyle Cobarrubias, Shinichi Oka, Zabrina L. Brumme, Kinh Van Nguyen, and Masafumi Takiguchi, (*Equal contribution)
  • Journal Title: AIDS Volume: 30 Issue: 5 Pages: 681-689
  • DOI: 10.1097/qad.0000000000000969
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Incidence of AIDS-Defining Opportunistic Infections and Mortality during Antiretroviral Therapy in a Cohort of Adult HIV-Infected Individuals in Hanoi (2016)
  • Author(s): Tanuma J, Lee KH, Haneuse S, Matsumoto S, Nguyen DT, Nguyen DT, Do CD, Pham TT, Nguyen KV, Oka S
  • Journal Title: PLoS One. Volume: 11 Issue: 3 Pages: e0150781-e0150781
  • DOI: 10.1371/journal.pone.0150781
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations (2015)
  • Author(s): Nozomi Kuse*, Mohammad Arif Rahman*, Hayato Murakoshi*, Giang Van Tran, Takayuki Chikata, Madoka Koyanagi, Kinh Van Nguyen, Hiroyuki Gatanaga, Shinichi Oka, and Masafumi Takiguchi, (*Equal contribution)
  • Journal Title: Journal of Virology Volume: 89 Issue: 14 Pages: 7363-7372
  • DOI: 10.1128/jvi.00974-15
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] CTL- and NK cell-mediated HIV-1 control in Asians (2018)
  • Author(s): Takiguchi Masafumi
  • Organizer: 19th Kumamoto AIDS Seminar
  • Int'l Joint Research
• [Presentation] Control of HIV-1 by CD8+ T cells specific for epitopes of conserved mosaic vaccine immunogens (2018)
  • Author(s): Murakoshi Hayato、Zou Chengcheng、Kuse Nozomi、Akahoshi Tomohiro、Chikata Takayuki、Gatanaga Hiroyuki、Oka Shinichi、Hanke Tomas、Takiguchi Masafumi
  • Organizer: HIVR4P 2018
  • Int'l Joint Research
• [Presentation] HLA class I - mediated HIV - 1 control in Vietnamese infected with HIV subtype A/E, National Scientific Conference on Infectious Diseases, HIV/AIDS (2018)
  • Author(s): Takiguchi Masafumi
  • Organizer: The 8th ASEAN Conference of Tropical Medicine and Parasitology
  • Int'l Joint Research / Invited
• [Presentation] HLA class I-mediated HIV-1 control in Vietnamese infected with HIV-1 subtype A/E (2018)
  • Author(s): Takiguchi M, Chikata T, Tran GV, Murakoshi H, Akahoshi T, Qi Y, Naranbhai V, Kuse N, Tamura Y, Koyanagi M, Sakai S, Nguyen DH, Nguyen DT, Nguyen HT, Nguyen TV, Oka S, Martin MP, Carrington M, Sakai K, Nguyen KV
  • Organizer: 20th International Conference on Emerging Infectious Diseases in the Pacific Rim /U.S.-Japan Cooperative Medical Sciences Program: AIDS and Immunology Joint Panel
  • Int'l Joint Research / Invited
• [Presentation] Long-term viral suppression and immune recovery during the initial antiretroviral therapy: results from a cohort of adult HIV-infected individuals in Hanoi, Vietnam (2017)
  • Author(s): Tanuma J, Matsumoto S, Haneuse S, Nguyen DT, Nguyen DT, Do CD, Cosimi LA, Pham TT, Nguyen KV, Oka S
  • Organizer: The annual Conference on Retroviruses and Opportunistic Infections (CROI)
  • Place of Presentation: Washington State Convention Center, USA
  • Year and Date: 2017-02-13
  • Int'l Joint Research
• [Presentation] 日本人およびベトナム人HIV-1感染者の病態進行の抑制に関与する細胞傷害性T細胞 (2017)
  • Author(s): 近田 貴敬, 村越 勇人, 潟永 博之, 岡 慎一, 滝口 雅文
  • Organizer: 第31回日本エイズ学会学術集会・総会（シンポジウム）
  • Invited
• [Presentation] ベトナム人HIV-1サブタイプA/E感染者コホートにおける、エイズ病態進行に関与するHLAアリルおよびHLA関連HIV-1多型のエイズ病態進行に及ぼす影響 (2017)
  • Author(s): 近田 貴敬, Tran Van Giang, 村越 勇人, 田村 美子, 赤星 智寛, 久世 望, 阪井 恵子, 小柳 円, Kinh Van Nguyen, 滝口 雅文
  • Organizer: 第31回日本エイズ学会学術集会・総会
• [Presentation] HLA class I-mediated HIV-1 control in Vietnamese infected with HIV-1 subtype A/E (2017)
  • Author(s): Chikata T, Tran GV, Murakoshi H, Akahoshi T, Kuse N, Qi Y, Tamura Y, Koyanagi M, Sakai S, Nguyen DH, Nguyen DT, Nguyen HT, Nguyen TV, Oka S, Carrington M, Sakai K, Nguyen KV, Takiguchi M
  • Organizer: 18th Kumamoto AIDS Seminar
  • Int'l Joint Research
• [Presentation] Identification of a detrimental HLA haplotype and the effect of its associated HIV-1 mutations in HIV-1 subtype A/E-infected Vietnamese (2017)
  • Author(s): Chikata T, Murakoshi H, Akahoshi T, Kuse N, Tamura Y, Sakai K, Takiguchi M
  • Organizer: 第65回日本ウイルス学会学術集会
• [Presentation] ベトナム人HIV-1サブタイプA/E感染者コホートにおけるエイズ病態進行に関与するHLAアリルの探索 (2016)
  • Author(s): 近田 貴敬, Giang Van Tran, 村越 勇人, 田村 美子, 赤星 智寛, 久世 望, 阪井 恵子, 小柳 円, Kinh Van Nguyen, 滝口 雅文
  • Organizer: 第30回日本エイズ学会学術集会・総会
  • Place of Presentation: かごしま県民交流センター, 日本
  • Year and Date: 2016-11-24
• [Presentation] Impact of a Single HLA-A*24:02-associated Escape Mutation on HLA-B*35:01-associated HIV-1 Control and T cell Adaptation (2016)
  • Author(s): Takayuki Chikata, Giang Van Tran, Hayato Murakoshi, Yoshiko Tamura, Tomohiro Akahoshi, Nozomi Kuse, Keiko Sakai, Kinh Van Nguyen, and Masafumi Takiguchi
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター, 日本
  • Year and Date: 2016-10-23
• [Presentation] Identification of HLA-associated polymorphisms in a cohort of HIV-1 subtype A/E infection (2015)
  • Author(s): Tran Van Giang, Takayuki Chikata, Yoshiko Tamura, Tomohiro Akahoshi, Hayato Murakoshi, Nozomi Kuse, Shinichi Oka, Keiko Sakai, Nguyen Van Kinh, Masafumi Takiguchi
  • Organizer: The 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015)
  • Place of Presentation: Vancouver Convention Centre (Vancouver, BC, Canada)
  • Year and Date: 2015-07-19
  • Int'l Joint Research
• [Remarks] 熊本大学ヒトレトロウイルス学共同研究センター国際連携分野
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/default.html
• [Remarks] 熊本大学エイズ学研究センター滝口プロジェクト研究室
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/viral/gyouseki/bib02/ronbun2017-2018.htm
• [Remarks] 熊本大学エイズ学研究センター滝口プロジェクト研究室
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/viral/gyouseki/bib02/ronbun2015-2016.htm
• [Remarks] 滝口プロジェクト研究室ホームページ
  • URL: http://www.caids.kumamoto-u.ac.jp/data/takiguchi/